rs4149339

Variant names:

• chr9-104782875-G-A
• rs4149339
• NM_005502.4:c.*1440C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005502.4(ABCA1):​c.*1440C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 149,952 control chromosomes in the GnomAD database, including 8,824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (8810 hom., cov: 30)
  • Exomes 𝑓: 0.31 (14 hom.)
• Consequence: ABCA1 NM_005502.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.73
• Publications: 20 publications found

Genes affected

ABCA1 (HGNC:29): (ATP binding cassette subfamily A member 1) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. With cholesterol as its substrate, this protein functions as a cholesteral efflux pump in the cellular lipid removal pathway. Mutations in both alleles of this gene cause Tangier disease and familial high-density lipoprotein (HDL) deficiency. [provided by RefSeq, Sep 2019]

NIPSNAP3B (HGNC:23641): (nipsnap homolog 3B) NIPSNAP3B belongs to a family of proteins with putative roles in vesicular trafficking (Buechler et al., 2004 [PubMed 15177564]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 9-104782875-G-A is Benign according to our data. Variant chr9-104782875-G-A is described in ClinVar as Benign. ClinVar VariationId is 364351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005502.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	NM_005502.4	MANE Select	c.*1440C>T		3_prime_UTR	Exon 50 of 50	NP_005493.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	ENST00000374736.8	TSL:1 MANE Select	c.*1440C>T		3_prime_UTR	Exon 50 of 50	ENSP00000363868.3
	ABCA1	ENST00000678995.1		c.*1440C>T		3_prime_UTR	Exon 50 of 50	ENSP00000504612.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 49275 AN: 149466 Hom.: 8791 Cov.: 30

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.310

GnomAD4 exome AF: 0.306 AC: 125 AN: 408 Hom.: 14 Cov.: 0 AF XY: 0.268 AC XY: 66 AN XY: 246

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.308 AC: 124 AN: 402

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.330 AC: 49331 AN: 149544 Hom.: 8810 Cov.: 30 AF XY: 0.333 AC XY: 24207 AN XY: 72730

African (AFR) AF: 0.376 AC: 15277 AN: 40592

American (AMR) AF: 0.382 AC: 5756 AN: 15080

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 639 AN: 3458

East Asian (EAS) AF: 0.757 AC: 3895 AN: 5142

South Asian (SAS) AF: 0.343 AC: 1632 AN: 4764

European-Finnish (FIN) AF: 0.292 AC: 2817 AN: 9650

Middle Eastern (MID) AF: 0.257 AC: 73 AN: 284

European-Non Finnish (NFE) AF: 0.271 AC: 18334 AN: 67602

Other (OTH) AF: 0.317 AC: 655 AN: 2068

Alfa AF: 0.293 Hom.: 27548

Bravo AF: 0.340

Asia WGS AF: 0.572 AC: 1984 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hypoalphalipoproteinemia, primary, 1 (1)
-	-	1	Tangier disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.083
DANN	Benign	0.33
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4149339; hg19: chr9-107545156;